The majority of murine skin tumors induced by ultraviolet radiation (UVR) are immunologically rejected following their transplantation to normal syngeneic animals. These same regressor (RE) phenotype tumors, however, are fully capable of progressive growth when inoculated into UVR-exposed recipients. Gaining insight into the cellular and molecular mechanisms responsible for the immunomodulatory influences of UVR has attracted a considerable degree of research attention over the past decade. In fact, much of our current appreciation of the immunobiology of skin, and the entire field of photoimmunology evolved from these early studies in experimental photocarcinogenesis. It is now apparent that an elucidation of the molecular characteristics which differentiate RE tumors from those capable of progressive growth in immunologically normal animals represents an important and unresolved issue in this model system. We recently have determined that all RE- phenotype tumors increase their surface expression of MHC Class I molecules in response to stimulation with gamma -interferon (gamma IFN). This is consistent with the reported effects of gamma IFN on normal cell types. Most progressor (PRO) phenotype UVR-tumors, however, lack this response to gamma IFN and do not increase their surface expression of MHC Class I molecules. This simple observation may represent an essential and unappreciated component of the host-tumor interrelationship associated with UVR carcinogenesis. This is especially important considering that Class I molecules serve as restriction elements for T-lymphocytes. We believe that this same finding may also prove to have direct clinical relevance in human host-tumor interrelationships. We have proposed in this application to a) test the hypothesis that a lack of responsiveness to gamma IFN can be directly related to tumor virulence, b) determine the underlying mechanisms responsible for gamma IFN sensitivity and investigate possible means of pharmacologic intervention, and c) determine whether RE-phenotype tumors gain their advantage in UVR- exposed recipients because of a depressed capacity by these hosts to promote a functional MHC Class I enhancing response. This will be accomplished experimentally by a) analyzing a number of distinct RE and PRO tumors as well as PRO greater than RE variants and RE greater than PRO variants, b) thoroughly evaluating the biochemical differences between RE and PRO tumors following gamma IFN stimulation, and c) determining whether UVR-exposed animals are capable of stimulating gamma IFN or IFN responses normally.